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Correlation of IL-31 serum levels with severity of atopic dermatitis
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“IL-31 is a prominent pruritogenic cytokine produced by infiltrating TH2 cells in AD and correlates with disease severity97,184,185.”
From Atopic dermatitis: an expanding therapeutic pipeline for a complex disease (2022) · cites this paper as [185]
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Interleukin 31, a cytokine produced by activated T cells, induces dermatitis in mice
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IL-31: A new link between T cells and pruritus in atopic skin inflammation
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Pathophysiology of pruritus in atopic dermatitis: an overview
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Self-citationInvolvement of IL‐31 on scratching behavior in NC/Nga mice with atopic‐like dermatitis
Takaoka, A., Arai, I., Sugimoto, M., Honma, Y., Futaki, N., Nakamura, A., & Nakaike, S. (2006) · Experimental Dermatology · doi:10.1111/j.1600-0625.2006.00405.x · Cited by 152
Expression of IL-31 gene transcripts in NC/Nga mice with atopic dermatitis
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A common haplotype of the IL-31 gene influencing gene expression is associated with nonatopic eczema
Schulz, F., Marenholz, I., Fölster‐Holst, R., Chen, C. I.-U., Sternjak, A., Baumgrass, R., Esparza-Gordillo, J., Grüber, C., Nickel, R. G., Schreiber, S., et al. (2007) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2007.07.065 · Cited by 81
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Atopic dermatitis: a disease of altered skin barrier and immune dysregulation
Boguniewicz, M., & Leung, D. Y. M. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2011.01027.x · Cited by 1,100
“Irrespective of the atopic phenotype, serum IL-31 levels have been shown to correlate with disease activity in AD (100).”
BackgroundInterleukins, from 1 to 37, and interferon-γ: Receptors, functions, and roles in diseases
Akdiş, M., Bürgler, S., Crameri, R., Eiwegger, T., Fujita, H., Alcaide, E. G., Klunker, S., Meyer, N., O’Mahony, L., Palomares, Ó., et al. (2011) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2010.11.050 · Cited by 809
Th2 Cytokines and Atopic Dermatitis
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“Serum IL-31 levels are also increased and there is a significant correlation with disease severity in both adults and children [129,130].”
BackgroundAtopic dermatitis: an expanding therapeutic pipeline for a complex disease
Bieber, T. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00266-6 · Cited by 623
Cellular and molecular immunologic mechanisms in patients with atopic dermatitis
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“17,142 Because IL-31 induces delayed onset of pru-ritus, it can actually be caused through an indirect mechanism.”
Self-citationEnvironmental risk factors and their role in the management of atopic dermatitis
Kantor, R. W., & Silverberg, J. I. (2016) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2016.1212660 · Cited by 387
“On the other hand, AD has been found to be associated with variants of a number of genes primarily involved in immune pathways, including IL-4R, IL-18, IL-31, etc. [14–16] The complex immune dysregulation in AD is increasingly being recognized.”
BackgroundInfluentialMediators of Chronic Pruritus in Atopic Dermatitis: Getting the Itch Out?
Mollanazar, N. K., Smith, P. K., & Yosipovitch, G. (2015) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-015-8488-5 · Cited by 354
“In addition, IL-31 levels positively correlate with disease severity in AD and with itch severity in CTCL [125, 126].”
BackgroundBiomarkers in atopic dermatitis—a review on behalf of the International Eczema Council
Renert-Yuval, Y., Thyssen, J. P., Bissonnette, R., Bieber, T., Kabashima, K., Hijnen, D., & Guttman-Yassky, E. (2021) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2021.01.013 · Cited by 350
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Recent insights into atopic dermatitis and implications for management of infectious complications
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“Recent data provide evidence that, irrespective of the atopic phenotype, serum IL-31 levels correlate with disease activity in patients with AD.(51) Importantly, staphylococcal SAgs have been shown to rapidly induce IL31 mRNA expression in the skin of atopic subjects in vivo and in PBMCs in vitro, suggesting that chro…”
BackgroundIL-31 regulates differentiation and filaggrin expression in human organotypic skin models
Cornelissen, C., Marquardt, Y., Czaja, K., Wenzel, J., Frank, J., Lüscher‐Firzlaff, J., Lüscher, B., & Baron, J. M. (2011) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2011.10.042 · Cited by 293
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“These higher levels are correlated with serum IgE, disease severity, and subjective itch intensity [5,17,21,52,53].”
BackgroundWerfel, T. (2009) · Journal of Investigative Dermatology · doi:10.1038/jid.2009.71 · Cited by 252
“In humans, IL-31 is significantly overexpressed in itching skin inflammation such as AD (Sonkoly et al., 2006; Raap et al., 2008).”
BackgroundSelf-citationEmerging role of interleukin‐31 and interleukin‐31 receptor in pruritus in atopic dermatitis
Furue, M., Yamamura, K., Kido‐Nakahara, M., Nakahara, T., & Fukui, Y. (2018) · Allergy · doi:10.1111/all.13239 · Cited by 240
“In addition, the serum levels of IL-31 are significantly increased in AD compared to healthy controls and are correlated with the severity of pediatric and adult AD.(69,70) The levels of IL-”
BackgroundInfluentialChapter 3 Cellular and Molecular Mechanisms in Atopic Dermatitis
Oyoshi, M. K., He, R., Kumar, L., Yoon, J., & Geha, R. S. (2009) · Advances in immunology · doi:10.1016/s0065-2776(09)01203-6 · Cited by 247
“There is a correlation between IL-31 serum levels with the severity of AD (Raap et al., 2008).”
BackgroundGenetic and epigenetic studies of atopic dermatitis
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The histamine H4 receptor is functionally expressed on TH2 cells
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Self-citationTRPA1-Dependent Pruritus in IL-13–Induced Chronic Atopic Dermatitis
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“The IL-31 serum level correlates with the disease severity [172].”
BackgroundThe interplay between genetic and environmental factors in the pathogenesis of atopic dermatitis
Otsuka, A., Nomura, T., Rerknimitr, P., Seidel, J. A., Honda, T., & Kabashima, K. (2017) · Immunological Reviews · doi:10.1111/imr.12545 · Cited by 188
The IL-4, IL-13 and IL-31 pathways in atopic dermatitis
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“Further, we found a significant correlation of IL-31 serum levels with SCORAD score in the extrinsic as well as in the intrinsic type of atopic dermatitis (3).”
BackgroundMethodSelf-citationIL-31: A new key player in dermatology and beyond
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Peripheral itch sensitization in atopic dermatitis
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IL-31 Expression by Inflammatory Cells is Preferentially Elevated in Atopic Dermatitis
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“In humans, IL-31 serum levels are higher in AD eompared with non-atopie healthy eontrols, and eorrelate with disease aetivity (14).”
BackgroundInterleukin‐31 and interleukin‐31 receptor: New therapeutic targets for atopic dermatitis
Nakashima, C., Otsuka, A., & Kabashima, K. (2018) · Experimental Dermatology · doi:10.1111/exd.13533 · Cited by 154
Human mast cells and basophils—How are they similar how are they different?
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Interleukin‐31: its role in canine pruritus and naturally occurring canine atopic dermatitis
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“Several investigators interested in the role of IL-31 in human AD have already extended their evaluations to the protein level and have generated data correlating serum levels of IL-31 to disease severity.(3,7) Specifically, studies have shown IL-31 to be elevated in the serum of human AD patients compared with health…”
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Self-citationInterleukin-31 is associated with uremic pruritus in patients receiving hemodialysis
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“IL-31 is also increased in the serum of AD patients [43,67], and increased blood levels of this itch-promoting cytokine positively correlate with disease severity [43,44].”
BackgroundHuman basophils are a source of ‐ and are differentially activated by ‐ IL‐31
Raap, U., Gehring, M., Kleiner, S., Rüdrich, U., Eiz‐Vesper, B., Haas, H., Kapp, A., & Gibbs, B. F. (2016) · Clinical & Experimental Allergy · doi:10.1111/cea.12875 · Cited by 120
Self-citationThe Role of Cytokines/Chemokines in the Pathogenesis of Atopic Dermatitis
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Emerging concepts: mast cell involvement in allergic diseases
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Role of the Pruritic Cytokine IL-31 in Autoimmune Skin Diseases
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Self-citationPrurigo Nodularis and Its Management
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Self-citationDistribution of IL-31 and its receptor expressing cells in skin of atopic dermatitis
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“In terms of the systemic expression of IL-31, serum levels were higher in AD patients than in the non-atopic healthy individuals and correlated with disease activity [12].”
Topical Therapies for Pruritus
Elmariah, S. B., & Lerner, E. A. (2011) · Seminars in Cutaneous Medicine and Surgery · doi:10.1016/j.sder.2011.04.008 · Cited by 107
The Infectious Aspects of Atopic Dermatitis
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“SEB has also been shown to induce lymphocyte expression of IL-31 [56], and this correlates with increased severity of AD [57].”
BackgroundFunctional effects of interleukin 31 in human primary keratinocytes
Kasraie, S., Niebuhr, M., Baumert, K., & Werfel, T. (2011) · Allergy · doi:10.1111/j.1398-9995.2011.02545.x · Cited by 99
“Recently, we provided evidence that serum IL-31 levels were significantly higher in patients with AD and correlated with disease activity in AD (9).”
BackgroundSelf-citationWong, C. K., Leung, K. M.-L., Qiu, H., Chow, J. L., Choi, A. O. K., & Lam, C. W.-K. (2012) · PLoS ONE · doi:10.1371/journal.pone.0029815 · Cited by 99
“compared to healthy individuals [7], and correlated positively with disease severity [8].”
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Self-citationPathophysiology of itch and new treatments
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Self-citationItch in dermatomyositis: the role of increased skin interleukin-31
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“with disease severity in adult and childhood AD [188, 189].”
BackgroundReceptors, cells and circuits involved in pruritus of systemic disorders
Kremer, A. E., Feramisco, J. D., Reeh, P. W., Beuers, U. H., & Elferink, R. P. J. O. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.02.007 · Cited by 97
Increased levels of serum IL‐31 in chronic spontaneous urticaria*
Raap, U., Wieczorek, D., Gehring, M., Pauls, I., Ständer, S., Kapp, A., & Wedi, B. (2010) · Experimental Dermatology · doi:10.1111/j.1600-0625.2010.01067.x · Cited by 93
Self-citationThe pathogenesis of Prurigo nodularis – ‘Super‐Itch’ in exploration
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“In addition, IL-31 can also be found in the circulatory system, as patients with atopic dermatitis have IL-31 serum levels correlating with disease severity and Th2 cytokines (Raap et al., 2008).”
BackgroundSelf-citationInterleukin-31 promotes fibrosis and T helper 2 polarization in systemic sclerosis
Kuzumi, A., Yoshizaki, A., Matsuda, K. M., Kotani, H., Norimatsu, Y., Fukayama, M., Ebata, S., Fukasawa, T., Yoshizaki‐Ogawa, A., Asano, Y., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26099-w · Cited by 89
Interleukin-31: A Novel Diagnostic Marker of Allergic Diseases
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Increased plasma IL-17, IL-31, and IL-33 levels in chronic spontaneous urticaria
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IL-31 is crucial for induction of pruritus, but not inflammation, in contact hypersensitivity
Takamori, A., Nambu, A., Sato, K., Yamaguchi, S., Matsuda, K., Numata, T., Sugawara, T., Yoshizaki, T., Arae, K., Morita, H., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-25094-4 · Cited by 85
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“Another cytokine correlating with disease severity in patients with AD is the pruritogenic IL-31 (Raap et al., 2008; Raap et al., 2012).”
BackgroundSelf-citationEosinophils are a Major Source of Interleukin-31 in Bullous Pemphigoid
Rüdrich, U., Gehring, M., Papakonstantinou, E., Illerhaus, A., Engmann, J., Kapp, A., Hartmann, K., Meyer, N. H., Gibbs, B. F., & Raap, U. (2018) · Acta Dermato Venereologica · doi:10.2340/00015555-2951 · Cited by 82
Self-citationYamamura, K., Uruno, T., Shiraishi, A., Tanaka, Y., Ushijima, M., Nakahara, T., Watanabe, M., Kido‐Nakahara, M., Tsuge, I., Furue, M., et al. (2017) · Nature Communications · doi:10.1038/ncomms13946 · Cited by 82
“In addition, in patients with AD, IL-31 is expressed by cutaneous lymphocyte antigen-positive skin homing CD4 þ T cells 18,20 , and serum IL-31 levels have been shown to correlate with the disease activity 21 .”
Singh, B. B., Jegga, A. G., Shanmukhappa, K. S., Edukulla, R., Khurana, G. H., Medvedovic, M., Dillon, S. R., & Madala, S. K. (2016) · PLoS ONE · doi:10.1371/journal.pone.0161877 · Cited by 81
“Serum IL-31 level was found to be significantly elevated in AD patients as compared to healthy controls [31, 32].”
BackgroundNew and emerging treatments for inflammatory itch
Erickson, S., Heul, A. V., & Kim, B. S. (2021) · Annals of Allergy, Asthma & Immunology · doi:10.1016/j.anai.2020.05.028 · Cited by 79
Control of the Physical and Antimicrobial Skin Barrier by an IL-31–IL-1 Signaling Network
Hänel, K. H., Pfaff, C. M., Cornelissen, C. G., Amann, P. M., Marquardt, Y., Czaja, K., Kim, A. L., Lüscher, B., & Baron, J. M. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1402943 · Cited by 77
A Modular View of Cytokine Networks in Atopic Dermatitis
Carmi-Levy, I., Homey, B., & Soumelis, V. (2011) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-010-8239-6 · Cited by 78
Serum IL-31 Levels are Increased in Patients with Cutaneous T-cell Lymphoma
Ohmatsu, H., Sugaya, M., Suga, H., Morimura, S., Miyagaki, T., Kai, H., Kagami, S., Fujita, H., Asano, Y., Tada, Y., et al. (2012) · Acta Dermato Venereologica · doi:10.2340/00015555-1345 · Cited by 75
Kasutani, K., Fujii, E., Ohyama, S., Adachi, H., Hasegawa, M., Kitamura, H., & Yamashita, N. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12823 · Cited by 73
“Serum IL-31 levels also increase in AD and there is a significant correlation with disease severity (Raap et al., 2008; Ezzat et al., 2011).”
BackgroundHuman Th2 but Not Th9 Cells Release IL-31 in a STAT6/NF-κB–Dependent Way
Maier, E., Werner, D., Duschl, A., Bohle, B., & Horejs‐Hoeck, J. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1301836 · Cited by 67
“Although there is convincing evidence that IL-31 induces proinflammatory cytokines, and there is a clear correlation between IL-31 level and disease severity in atopic skin disorders (13, 15, 42, 43), further observations are needed to elucidate the definite role of IL-31 in allergic inflammation.”
BackgroundLee, C., Hong, C., Yu, W.-T., Chuang, H., Huang, S. K., Chen, G., Yoshioka, T., Sakata, M., Liao, W., Ko, Y., et al. (2012) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2012.11047.x · Cited by 68
Emerging Treatment Options in Atopic Dermatitis: Systemic Therapies
Nygaard, U., Vestergaard, C., & Deleuran, M. S. (2017) · Dermatology · doi:10.1159/000484406 · Cited by 67
Hartmann, K., Wagner, N., Rabenhorst, A., Pflanz, L., Leja, S., Förster, A., Gehring, M., Kapp, A., & Raap, U. (2012) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2012.11.008 · Cited by 67
Self-citationIL-31 Serum Protein and Tissue mRNA Levels in Patients with Atopic Dermatitis
Kim, S. J., Kim, H. J., Yang, H. S., Kim, E., Huh, I., & Yang, J.-M. (2011) · Annals of Dermatology · doi:10.5021/ad.2011.23.4.468 · Cited by 66
“In previous study, Raap et al.19 found that serum IL-31 levels were significantly higher in both ADe and ADi patients, without any difference between AD subgroups, and also showed that SCORAD score was significantly correlated with serum IL-31 level in all AD patients.”
ResultGonzales, A. J., Fleck, T. J., Humphrey, W. R., Galvan, B. A., Aleo, M. M., Mahabir, S. P., Tena, J., Greenwood, K. G., & McCall, R. B. (2015) · Veterinary Dermatology · doi:10.1111/vde.12280 · Cited by 66
Chronic Pruritus: Current and Emerging Treatment Options
Pereira, M. P., & Ständer, S. (2017) · Drugs · doi:10.1007/s40265-017-0746-9 · Cited by 66
“Interleukin-31 released by CD4? T cells and T helper-2 cells plays a central role in pruritus transmission in inflammatory pruritic conditions [47] and thus constitutes a relevant target [48].”
BackgroundSelf-citationStänder, S., Raap, U., Weißhaar, E., Schmelz, M., Mettang, T., Handwerker, H. O., & Luger, T. A. (2011) · JDDG Journal der Deutschen Dermatologischen Gesellschaft · doi:10.1111/j.1610-0387.2011.07585.x · Cited by 65
Self-citationMast cells and basophils in cutaneous immune responses
Otsuka, A., & Kabashima, K. (2014) · Allergy · doi:10.1111/all.12526 · Cited by 67
Pruritus in Autoimmune and Inflammatory Dermatoses
Zeidler, C., Pereira, M. P., Huet, F., Misery, L., Steinbrink, K., & Ständer, S. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01303 · Cited by 62
“This was surprising, because IL31 levels are increased in other pruritic dermatoses like AD (58) and psoriasis vulgaris (59).”
BackgroundSelf-citation25-Hydroxyvitamin D, IL-31, and IL-33 in Children with Allergic Disease of the Airways
Bonanno, A., Gangemi, S., Grutta, S. L., Malizia, V., Riccobono, L., Colombo, P., Cibella, F., & Profita, M. (2014) · Mediators of Inflammation · doi:10.1155/2014/520241 · Cited by 61
“Plasma IL-31 concentration was found to be significantly elevated in patients with atopic dermatitis (AD) compared to healthy individuals [18] and positively correlated with disease severity [19].”
BackgroundEndotypes of atopic dermatitis
Fyhrquist, N., Yang, Y., Karisola, P., & Alenius, H. T. (2025) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2025.02.029 · Cited by 65
Oyama, S., Kitamura, H., Kuramochi, T., Higuchi, Y., Matsushita, H., Suzuki, T., Goto, M., Adachi, H., Kasutani, K., Sakamoto, A., et al. (2016) · Experimental Dermatology · doi:10.1111/exd.13236 · Cited by 57
Exploring the Role of Staphylococcus Aureus Toxins in Atopic Dermatitis
Yoshikawa, F. S. Y., de Lima, J. F., Sato, M. N., Ramos, Y. Á. L., Aoki, V., & Orfali, R. L. (2019) · Toxins · doi:10.3390/toxins11060321 · Cited by 60
“IL-31 is a Th2 cytokine associated with AD severity and pruritus [80,81].”
BackgroundMalignancy‐associated pruritus
Rowe, B., & Yosipovitch, G. (2015) · European Journal of Pain · doi:10.1002/ejp.760 · Cited by 56
Altrichter, S., Hawro, T., Hänel, K. H., Czaja, K., Lüscher, B., Maurer, M., Church, M. K., & Baron, J. M. (2014) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/jdv.12831 · Cited by 56
Atopic eczema or atopiform dermatitis
Bos, J. D., Brenninkmeijer, E. E. A., Schram, M. E., Middelkamp-Hup, M. A., Spuls, P. I., & Smitt, J. H. S. (2010) · Experimental Dermatology · doi:10.1111/j.1600-0625.2009.01024.x · Cited by 56
Atopic Dermatitis: Striving for Reliable Biomarkers
Mastraftsi, S., Vrioni, G., Bakakis, M., Nicolaidou, E., Rigopoulos, D., Stratigos, A., & Gregoriou, S. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11164639 · Cited by 59
Cytokine modulation of atopic itch
Trier, A. M., & Kim, B. (2018) · Current Opinion in Immunology · doi:10.1016/j.coi.2018.05.005 · Cited by 55
“Patients with AD have increased cutaneous expression of IL-31 and disease activity has also been found to correlate with serum levels of IL-31 [18,19].”
BackgroundPetra, A. I., Tsilioni, I., Taracanova, A., Katsarou‐Katsari, A., & Theoharides, T. C. (2018) · Allergy and Asthma Proceedings · doi:10.2500/aap.2018.38.4105 · Cited by 54
“Moreover, serum levels of IL-31 were increased and correlated with disease severity in AD.(27,28) In fact, IL-31 was shown to induce dermatitis in mice.”
BackgroundInfluentialInterleukin-31 expression and relation to disease severity in human asthma
Lai, T., Wu, D., Li, W., Chen, M., Yi, Z.-N., Huang, D. A., Jing, Z., Lü, Y., Lv, Q., Li, D., et al. (2016) · Scientific Reports · doi:10.1038/srep22835 · Cited by 52
“IL-31 signals through the heterodimeric receptor IL-31RA and OSMR, and has been linked with the development of atopic dermatitis 21 .”
Staphylococcal α-Toxin Induces a Higher T Cell Proliferation and Interleukin-31 in Atopic Dermatitis
Niebuhr, M., Mamerow, D., Heratizadeh, A., Satzger, I., & Werfel, T. (2011) · International Archives of Allergy and Immunology · doi:10.1159/000323905 · Cited by 50
Self-citation
Metadata
- Authors
- Raap, U., Wichmann, K., Bruder, M., Ständer, S., Wedi, B., Kapp, A., & Werfel, T.
- Affiliations
- Medizinische Hochschule Hannover (DE)
- University of Münster (DE)
- Corresponding author
- Raap, Ulrike
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2008-08
- Volume
- 122
- Issue
- 2
- Pages
- 421-423
- ISSN
- 0091-6749 (ISSN-L)
- OpenAlex
- W2083380164
- Cited by
- 299
- References
- 10
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 15 · 2023: 19 · 2022: 15 · 2021: 24 · 2020: 12 · 2019: 17 · 2018: 26 · 2017: 26 · 2016: 26 · 2015: 21 · 2014: 22 · 2013: 12 · 2012: 11
- FWCI
- 15.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Allergy and Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Food Allergy and Anaphylaxis Network
- European Commission
- Astellas Pharma
- Medizinischen Hochschule Hannover
- UCB Pharma
- Topics
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
- Health Sciences › Medicine › Dermatology › Contact Dermatitis and Allergies
- Keywords
- atopic dermatitis, IL-31, pruritus, disease severity, cytokines, scratching behavior, NC/Nga mice, T cells, quality of life, antipruritic therapy
- MeSH terms
- Adult, Dermatitis, Atopic, Humans, Interleukins, Middle Aged
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